Liraglutide improved the cognitive function of diabetic mice via the receptor of advanced glycation end products down-regulation

Abstract

Background and aims Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE), are associated with cognition decline. We aim to investigate the effect of liraglutide on cognitive function in diabetic mice. Results Diabetic mice showed decreased cognitive function. Moreover, lower glucagon like peptide-1 (GLP-1) levels in plasma were detected in db/db mice. Additionally, up-regulated RAGE and down-regulated glucagon like peptide-1 (GLP-1R) levels were observed in db/db mice. However, decreased GLP-1R and increased RAGE were reversed by liraglutide. We also found decreased cellular activity in cells with AGEs. Moreover, AGEs up-regulated RAGE in PC12 and HT22 cells. However, liraglutide improved the cell activity damaged by AGEs. Although we did not discover the direct-interaction between RAGE and GLP-1R, elevated RAGE levels induced by AGEs were restored by liraglutide. Conclusion We demonstrated that the cognitive function of diabetic mice was improved by liraglutide via the down-regulation of RAGE. Methods db/db mice and db/m mice were used in this study. Liraglutide was used to remedy diabetic mice. Neurons and RAGE in hippocampus were shown by immunofluorescence. And then, PC12 cells or HT22 cells with AGEs were treated with liraglutide. GLP-1R and RAGE were measured by western blotting.

Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis

“…AGEs has been widely recognized to be an inducer and promoter in diabetic complications [ 42 ]. To further investigate mechanism of TFA on protecting brain function, HT22 cell line was applied.…”

Systematic investigation of the underlying mechanisms of GLP-1 receptor agonists to prevent myocardial infarction in patients with type 2 diabetes mellitus using network pharmacology

“…Some researchers have provided evidence regarding the association between GLP-1RAs and the abovementioned results. GLP-1RAs, such as liraglutide and exenatide, attenuate RAGE expression in several cell types, especially under diabetic conditions ( Zhang et al, 2016 ; Zhang et al, 2017 ; Zhang et al, 2020 ), suggesting that the downregulation of RAGE represents a potential mechanism of GLP-1RAs against T2DM. In module two, RAS was a significant KEGG-enriched item.…”

Central GLP-1 contributes to improved cognitive function and brain glucose uptake after duodenum-jejunum bypass on obese and diabetic rats

“…Although the clinical findings are equivocal (57,58), the potential of GLP-1, its analogs, and agonist in enhancing brain function under diabetic conditions is certain (59)(60)(61)(62), this is undoubtedly a direct explanation for the changes following ICV injections of Lira and Exe-9. As a widely used analog of GLP-1, Lira is a synthetic activator highly homologous to natural GLP-1 with a dose-dependent effect on both glucose control (63) and weight loss (64) as a currently approved treatment for obesity, and it has been reported previously that Lira restores glucose transport at the BBB in humans (65).…”